Journal
CELL HOST & MICROBE
Volume 12, Issue 3, Pages 373-380Publisher
CELL PRESS
DOI: 10.1016/j.chom.2012.07.008
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Funding
- National Institutes of Health [R21 AI080364, R01 AI50529, R01 AI58715]
- Deutsche Forschungsgemeinschaft (DFG) [FA 378/11-1]
- Leibniz award
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The interferon-induced host restriction factor tetherin poses a barrier for SIV transmission from primates to humans. After cross-species transmission, the chimpanzee precursor of pandemic HIV-1 switched from the accessory protein Nef to Vpu to effectively counteract human tetherin. As we report here, the experimental reintroduction of HIV-1 into its original chimpanzee host resulted in a virus that can use both Vpu and Nef to antagonize chimpanzee tetherin. Functional analyses demonstrated that alterations in and near the highly conserved ExxxLL motif in the C-terminal loop of Nef were critical for the reacquisition of antitetherin activity. Strikingly, just two amino acid changes allowed HIV-1 Nef to counteract chimpanzee tetherin and promote virus release. Our data demonstrate that primate lentiviruses can reacquire lost accessory gene functions during a single in vivo passage and suggest that other functional constraints keep Nef ready to regain antitetherin activity.
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